SAFIR-I: Design and Performance of a High-Rate Preclinical PET Insert for MRI.

(1) Background: Small Animal Fast Insert for MRI detector I (SAFIR-I) is a preclinical Positron Emission Tomography (PET) insert for the Bruker BioSpec 70/30 Ultra Shield Refrigerated (USR) preclinical 7T Magnetic Resonance Imaging (MRI) system. It is designed explicitly for high-rate kinetic studies in mice and rats with injected activities reaching 500MBq, enabling truly simultaneous quantitative PET and Magnetic Resonance (MR) imaging with time frames of a few seconds in length. (2) Methods: SAFIR-I has an axial field of view of 54.2mm and an inner diameter of 114mm. It employs Lutetium Yttrium OxyorthoSilicate (LYSO) crystals and Multi Pixel Photon Counter (MPPC) arrays. The Position-Energy-Timing Application Specific Integrated Circuit, version 6, Single Ended (PETA6SE) digitizes the MPPC signals and provides time stamps and energy information. (3) Results: SAFIR-I is MR-compatible. The system's Coincidence Resolving Time (CRT) and energy resolution are between separate-uncertainty 209.0(3)ps and separate-uncertainty 12.41(02) Full Width at Half Maximum (FWHM) at low activity and separate-uncertainty 326.89(12)ps and separate-uncertainty 20.630(011) FWHM at 550MBq, respectively. The peak sensitivity is ∼1.6. The excellent performance facilitated the successful execution of first in vivo rat studies beyond 300MBq. Based on features visible in the acquired images, we estimate the spatial resolution to be ∼2mm in the center of the Field Of View (FOV). (4) Conclusion: The SAFIR-I PET insert provides excellent performance, permitting simultaneous in vivo small animal PET/MR image acquisitions with time frames of a few seconds in length at activities of up to 500MBq.

SAFIR-I: first NEMA NU 4-2008-based performance characterization.

BACKGROUND: Small Animal Fast Insert for MRI detector I (SAFIR-I) is a novel Positron Emission Tomography insert for a [Formula: see text] Bruker BioSpec 70/30 Ultra Shield Refrigerated Magnetic Resonance Imaging (MRI) system. It facilitates truly simultaneous quantitative imaging in mice and rats at injected activities as high as [Formula: see text]. Exploitation of the resulting high count rates enables quick image formation at few seconds per frame. In this investigation, key performance parameters of SAFIR-I have been determined according to the evaluations outlined in the National Electrical Manufacturers Association (NEMA) Standards Publication NU 4-2008 (NEMA-NU4) protocol. RESULTS: Using an energy window of 391 to [Formula: see text] and a Coincidence Timing Window of [Formula: see text], the following performance was observed: The average spatial resolution at [Formula: see text] radial offset (Full Width at Half Maximum) is [Formula: see text] when using Filtered Backprojection, 3D Reprojection reconstruction. For the mouse- and rat-like phantoms, the maximal Noise-Equivalent Count Rates (NECRs) are [Formula: see text] at the highest tested average effective concentration of [Formula: see text], and [Formula: see text] at the highest tested average effective concentration of [Formula: see text], respectively. The NECR peak is not yet reached for either of these cases. The peak sensitivity is [Formula: see text]. The Image Quality phantom uniformity standard deviation is [Formula: see text]. The Recovery Coefficient for the [Formula: see text] rod is [Formula: see text]. The Spill-Over Ratios are [Formula: see text] and [Formula: see text], for the water- and air-filled cylinder, respectively. An accuracy of [Formula: see text] was achieved for the quantitative calibration of reconstructed voxel values. CONCLUSIONS: The measured performance parameters indicate that the various design goals have been achieved. SAFIR-I offers excellent performance, especially at the high activities it was designed for. This facilitates planned experiments with fast tracer kinetics in small animals. Ways to potentially improve performance can still be explored. Simultaneously, further performance gains can be expected for a forthcoming insert featuring 2.7 times longer axial coverage named Small Animal Fast Insert for MRI detector II (SAFIR-II).

TRAIL-receptor 2-a novel negative regulator of p53.

TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2) can induce apoptosis in cancer cells upon crosslinking by TRAIL. However, TRAIL-R2 is highly expressed by many cancers suggesting pro-tumor functions. Indeed, TRAIL/TRAIL-R2 also activate pro-inflammatory pathways enhancing tumor cell invasion, migration, and proliferation. In addition, nuclear TRAIL-R2 (nTRAIL-R2) promotes malignancy by inhibiting miRNA let-7-maturation. Here, we show that TRAIL-R2 interacts with the tumor suppressor protein p53 in the nucleus, assigning a novel pro-tumor function to TRAIL-R2. Knockdown of TRAIL-R2 in p53 wild-type cells increases the half-life of p53 and the expression of its target genes, whereas its re-expression decreases p53 protein levels. Interestingly, TRAIL-R2 also interacts with promyelocytic leukemia protein (PML), a major regulator of p53 stability. PML-nuclear bodies are also the main sites of TRAIL-R2/p53 co-localization. Notably, knockdown or destruction of PML abolishes the TRAIL-R2-mediated regulation of p53 levels. In summary, our finding that nTRAIL-R2 facilitates p53 degradation and thereby negatively regulates p53 target gene expression provides insight into an oncogenic role of TRAIL-R2 in tumorigenesis that particularly manifests in p53 wild-type tumors.